Broadening the antiviral landscape for influenza A virus: Glycoprotein-targeted approaches to infection prevention and treatment

Abstract

The potential of influenza A virus (IAV) to evolve and cross species barriers keeps it at the forefront of public health concerns. The endemic seasonal viruses are associated with a consistently high disease burden, and zoonotic infections pose a continuous threat of sparking the next pandemic. Consequently, there is an urgent need for broadly protective solutions for the control of IAV, including both vaccines and antivirals. A detailed characterization of antigenic sites on the viral glycoproteins, informed by the study of broadly neutralizing antibodies, contributes to this understanding and is vital to inform vaccine design. This thesis explores the development of a nanoparticle-based vaccine candidate and the discovery of monoclonal antibodies targeting the less examined neuraminidase glycoprotein. Additionally, it introduces a novel approach for the targeting of a recognized site for broadly neutralizing antibodies in the stem domain of the other glycoprotein hemagglutinin using macrocyclic peptides, an emerging class of antiviral agents. This research offers additional insights and innovative strategies that could contribute to the development of more effective interventions against IAV.